title: Prognostic significance of β-human chorionic gonadotropin and PAX8 expression in anaplastic thyroid carcinoma.
abstract: BACKGROUND
  Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy with a median survival of five months. Multimodality treatment is associated with some improvement in survival, but patients are only infrequently curable. Although β-hCG secretion has been reported in many neoplasms, it has never been described in ATC. The objectives of this study were to report a case of β-hCG-secreting ATC and to study the expression and significance of β-hCG and PAX8 in an institutional cohort of ATC.
  
  
  METHODS
  The sentinel case was characterized and then immunohistochemistry was performed for β-hCG and PAX8 on 30 ATC patients. Clinical follow-up was obtained by chart review.
  
  
  RESULTS
  The sentinel patient with β-hCG-secreting ATC had a dramatic response to chemotherapy and radiation. After surgical excision of residual disease, the patient developed a regional recurrence of differentiated thyroid carcinoma at 18 months. However, she is now, 30 months after initial therapy, with no evidence of disease and no detectable serum β-hCG or thyroglobulin. Five of the 30 (17%) total ATCs were positive for β-hCG and 18 (60%) for PAX8. Outcomes for the β-hCG-positive cases were not significantly different from those for negative ones. However, none of the other four β-hCG-positive ATC patients received treatment with either chemotherapy or radiation. Interestingly, PAX8 positivity correlated with statistically significantly better overall survival (p=0.019).
  
  
  CONCLUSIONS
  β-hCG is expressed in a minority of ATCs. Although only a single case in the study had diffuse immunohistochemical expression, the response it showed to aggressive multimodality therapy and the resulting favorable outcome suggest that β-hCG-positive ATC may be a unique tumor subtype, or possibly even a unique entity. PAX8 is a useful marker of ATC and may be helpful in the differential diagnosis with other malignant neoplasms.
authors.affiliation: 1 Department of Pathology & Immunology, Washington University School of Medicine , St. Louis, Missouri.
authors.forename: Nils
authors.initials: N
authors.lastname: Becker
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Chernock
authors.forename: Brian
authors.initials: B
authors.lastname: Nussenbaum
authors.forename: James S
authors.initials: JS
authors.lastname: Lewis
mesh_terms: D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000096:biosynthesis*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis*; D011379:Prognosis; D013954:Thyroglobulin / Q000378:metabolism; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D013954:Thyroglobulin